Dr. Quinlivan continues her interest in virus-virus interactions by investigating the effect of human papillomavirus (HPV) on EBV replication. There is a potential for interaction between these two oncogenic viruses in vivo because both viruses can be recovered from dysplastic cervical tissue. Due to the high prevalence of cervical dysplasia and malignancy, any interactions discovered will have medically important implications. The Kenney laboratory has previously observed that an HPV gene product (possibly E6) acts in synergy with an EBV transactivator, Z, to activate the EBV early promoter, BMRF1. The first aim will be to confirm the preliminary observations and identify the HPV gene product responsible for this effect. Second, the effect of HPV on EBV replication in vitro will be determined, using cotransfections and immunoblots to look for a synergistic effect on EBV reactivation by HPV and Z. In the third specific aim she will characterize EBV gene expression and the replicative state of EBV in normal and dysplastic uterine cervical specimens, using genomic termini analyses and PCR amplification of latent, early and late messages. The transcriptional patterns which are identified will be correlated with the presence or absence of specific HPV types. Fourth, the mechanism by which HPV increases Z-induced transactivation will be determined by performing protein-DNA binding studies, and identifying the key domains of the transactivators and BMRF1 promoter. Fifth, she will examine the effect of the Z transactivator on the HPV regulatory region.